P574: DIAGNOSIS AND TREATMENT OF T/MYELOID MIXED PHENOTYPE ACUTE LEUKAEMIA (T/M-MPAL)- A UK SINGLE CENTRE EXPERIENCE
Authors: Enas Abusalim, Evan Vitsaras, Karen Orfinada, Baker Robert, Elisabeth Nacheva, Andrew Wilson, Jenny O’nions, Gupta Rajeev, Ke Xu
Journal: HemaSphere (2023)

Background: T/myeloid MPAL is a rare leukaemia subtype with poor prognosis. It is characterized by immunophenotypic features of both myeloid and T-lymphoid lineages. T/myeloid MPAL is distinct from T-cell acute lymphocytic leukaemia (T-ALL) and acute myeloid leukaemia (AML) but shares significant molecular and genomic similarity to early T-cell precursor-like ALL (ETP-ALL). Aims: We reviewed the immunophenotyping, molecular and cytogenetics profile of T/M-MPAL cases, their treatment and outcome in our single centre. Methods: A retrospective analysis was performed of all T/M-MPAL patients treated at University College London Hospital between February/2015 to April/2022. The diagnosis of T/M-MPAL was made in accordance with the WHO diagnostic criteria. We reviewed bone marrow immunophenotyping, myeloid next generation sequencing (NGS) (Archer VariantPlex& TruSight Illumina), QuanDx Q30 RT-PCR assay, fluorescence in situ hybridization (FISH), and molecular karyotyping (Agilent) results, patients’ treatment regimen and outcome. Response assessments were made as per European LeukemiaNet (ELN) criteria (Döhner et al., 2017). Results: A total of nine T/M-MPAL cases were identified among cases of leukaemia, with a median follow up of 8 months. Of the nine patients, seven patients were male and two were female. Median age was 23 years old (range 13-73 years). All patients blast populations had cCD3 (or CD3), MPO, CD34 and cCD34 expression by immunophenotyping. Myeloid marker CD117, CD13, and CD33 were positive in 66%, 88% and 88%, respectively. T lymphoid marker CD2, CD5, CD7 were positive in 55%, 44% and 100% respectively (Figure 1). The most common molecular abnormalities detected were WT1 (62%), NRAS/KRAS (37%), and BCOR (25%). Additional mutations detected were NOTCH, RUNX1, TP53, IKZF1, IDH1/2, and U2AF1. FLT3 TKD was mutated in 11% and FLT3 ITD in 22% patients (Figure 1). All nine patients had FISH. Probes used included KMT2A, CBFB-MYH11, RUNX1-RUNX1T1, BCR-ABL, TCRA/D, 5q, 7q, 20q and MECOM. Molecular karyotyping via chromosomal microarray was performed on six patients’ samples. Three patients’ samples had G-banding. One sample had complex karyotype with ETV6 rearrangement; one showed TCR rearrangement; one showed MLL amplification and 17p deletion; one had trisomy 4 and one had deletion TP53 with gain of 7q; the remaining four had a normal karyotyping. One patient was unfit for intensive chemotherapy and received azacitidine with palliative intent. Eight patients received Fla-Ida (fludarabine, cytarabine, idarubicin), Fla-Ida-venetoclax or mini-Fla-Ida as part of an induction regimen. One patient required a salvage regimen with venetoclax -azacitidine prior to achieving complete remission. Seven patients achieved complete remission and proceeded to receive allogeneic haematopoietic stem cell transplantation (alloHSCT). Two patients did not proceed to alloHSCT due to disease progression. The median overall survival for patients who underwent alloHSCT is not reached in this analysis. Summary/Conclusion: Our data identified genetic mutations in WT1, NOTCH1, RAS, FLT3, RUNX1, TP53, IKZF1, BCOR, ETV6, IDH1/2 and U2AF1, with WT1 as the most common mutation in our cohort of T/M-MPAL patients. Fla-Ida is effective to bridge to alloHSCT. The outcome of patients without alloHSCT is very poor.Keywords: Mixed lineage leukemia